The objective of this study was to assess the effects of phosphodiesterase type 2 (PDE2) and type 10 (PDE10) inhibition on memory function in the object recognition task using the scopolamine- and MK-801-induced memory deficit model. The effects of the PDE2 inhibitor BAY 60-7550 and the PDE10 inhibitor PQ-10 on object recognition performance were investigated in the scopolamine (0.1mg/kg, i.p.) or MK-801 (0.125 mg/kg, i.p.) model. BAY 60-7550 was tested at a dose of 0.3-3mg/kg (p.o.) in both models; PQ-10 was tested at doses of 0.1-1mg/kg (p.o.) in the scopolamine model and 0.3-3mg/kg in the MK-801 model. All compounds were injected 30 min before the learning trial. Both BAY 60-7550 (1mg/kg) and PQ-10 (0.3mg/kg) attenuated the scopolamine-induced memory deficit. The MK-801-induced memory deficit was reversed after treatment with each PDE inhibitor at a dose of 1mg/kg or higher. PQ10 was highly brain penetrant, whereas 60-7550 levels in the brain were very low after oral treatment. We concluded that since BAY 60-7550 and PQ10 reversed both scopolamine- and MK-801-induced memory deficits, this supports the notion that dual substrate PDE inhibitors might be suitable candidates for cognition enhancement.

译文

:本研究的目的是使用东pol碱和MK-801诱导的记忆缺陷模型评估2型磷酸二酯酶(PDE2)和10型(PDE10)抑制对物体识别任务中记忆功能的影响。在东pol碱(0.1mg / kg,i.p.)或MK-801(0.125 mg / kg,i.p.)模型中研究了PDE2抑制剂BAY 60-7550和PDE10抑制剂PQ-10对物体识别性能的影响。在两个模型中,BAY 60-7550的剂量为0.3-3mg / kg(p.o.)。在东pol碱模型中以0.1-1mg / kg(p.o.)的剂量测试PQ-10,在MK-801模型中以0.3-3mg / kg的剂量测试。在学习试验之前30分钟注射所有化合物。 BAY 60-7550(1mg / kg)和PQ-10(0.3mg / kg)均减弱了东pol碱诱导的记忆障碍。用每种PDE抑制剂以1mg / kg或更高的剂量治疗后,MK-801诱导的记忆缺陷得以逆转。 PQ10具有很高的脑渗透性,而口服治疗后脑中60-7550的水平非常低。我们得出的结论是,由于BAY 60-7550和PQ10逆转了东pol碱和MK-801诱导的记忆缺陷,因此支持以下观点:双底物PDE抑制剂可能是增强认知的合适候选者。

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